Modulation of CYP2E1 metabolic activity in a cohort of confirmed caffeine ingesting pregnant women with preterm offspring

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Abstract

Background

To ascertain interactions of caffeine ingestion, food, medications, and environmental exposures during preterm human gestation, under informed consent, we studied a cohort of Mexican women with further preterm offspring born at ≤ 34 completed weeks. At birth, blood samples were taken from mothers and umbilical cords to determine caffeine and metabolites concentrations and CYP1A2 (rs762551) and CYP2E1 (rs2031920, rs3813867) polymorphisms involved in caffeine metabolism.

Results

In 90 pregnant women who gave birth to 98 preterm neonates, self-informed caffeine ingestion rate was 97%, laboratory confirmed rate was 93 %. Theobromine was the predominant metabolite found. Consumption of acetaminophen correlated significantly with changes in caffeine metabolism (acetaminophen R ² = 0.637, p = 0.01) due to activation of CYP2E1 alternate pathways. The main caffeine source was cola soft drinks.

Conclusion

Environmental exposures, especially acetaminophen ingestion during human preterm pregnancy, can modulate CYP2E1 metabolic activity.

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Most cited references 27

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Caffeine therapy for apnea of prematurity.

Barbara Schmidt, Robin Roberts, Peter E Davis … (2006)

Methylxanthines reduce the frequency of apnea of prematurity and the need for mechanical ventilation during the first seven days of therapy. It is uncertain whether methylxanthines have other short- and long-term benefits or risks in infants with very low birth weight. We randomly assigned 2006 infants with birth weights of 500 to 1250 g during the first 10 days of life to receive either caffeine or placebo, until drug therapy for apnea of prematurity was no longer needed. We evaluated the short-term outcomes before the first discharge home. Of 963 infants who were assigned to caffeine and who remained alive at a postmenstrual age of 36 weeks, 350 (36 percent) received supplemental oxygen, as did 447 of the 954 infants (47 percent) assigned to placebo (adjusted odds ratio, 0.63; 95 percent confidence interval, 0.52 to 0.76; P<0.001). Positive airway pressure was discontinued one week earlier in the infants assigned to caffeine (median postmenstrual age, 31.0 weeks; interquartile range, 29.4 to 33.0) than in the infants in the placebo group (median postmenstrual age, 32.0 weeks; interquartile range, 30.3 to 34.0; P<0.001). Caffeine reduced weight gain temporarily. The mean difference in weight gain between the group receiving caffeine and the group receiving placebo was greatest after two weeks (mean difference, -23 g; 95 percent confidence interval, -32 to -13; P<0.001). The rates of death, ultrasonographic signs of brain injury, and necrotizing enterocolitis did not differ significantly between the two groups. Caffeine therapy for apnea of prematurity reduces the rate of bronchopulmonary dysplasia in infants with very low birth weight. (ClinicalTrials.gov number, NCT00182312.). Copyright 2006 Massachusetts Medical Society.

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Food sources and intakes of caffeine in the diets of persons in the United States.

Carol D Frary, Rachel K Johnson, Min Wang (2005)

This study provides information on the caffeine intakes of a representative sample of the US population using the US Department of Agriculture 1994 to 1996 and 1998 Continuing Survey of Food Intakes by Individuals. The percentage of caffeine consumers of the total sample (N=18,081) and by age and sex groups and for pregnant women were determined. Among caffeine consumers (n=15,716), the following were determined: mean intakes of caffeine (milligrams per day and milligrams per kilogram per day) for all caffeine consumers, as well as for each age and sex group and pregnant women; mean intakes (milligrams per day) of caffeine by food and beverage sources; and the percent contribution of each food and beverage category to total caffeine intake for all caffeine consumers, as well as each age and sex group and pregnant women. Eight-seven percent of the sample consumed food and beverages containing caffeine. On average, caffeine consumers' intakes were 193 mg caffeine per day and 1.2 mg caffeine per kilogram of body weight per day. As age increased, caffeine consumption increased among people aged 2 to 54 years. Men and women aged 35 to 64 years were among the highest consumers of caffeine. Major sources of caffeine were coffee (71%), soft drinks (16%), and tea (12%). Coffee was the major source of caffeine in the diets of adults, whereas soft drinks were the primary source for children and teens.

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Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption.

Hannia Campos, Ahmed-Abdalla El-Tantawy, Marilyn C. Cornelis (2007)

Caffeine is the most widely consumed stimulant in the world, and individual differences in response to its stimulating effects may explain some of the variability in caffeine consumption within a population. We examined whether genetic variability in caffeine metabolism [cytochrome P450 1A2 (CYP1A2) -163A-->C] or the main target of caffeine action in the nervous system [adenosine A(2A) receptor (ADORA2A) 1083C-->T] is associated with habitual caffeine consumption. Subjects (n=2735) were participants from a study of gene-diet interactions and risk of myocardial infarction who did not have a history of hypertension. Genotype frequencies were examined among persons who were categorized according to their self-reported daily caffeine intake, as assessed with a validated food-frequency questionnaire. The ADORA2A, but not the CYP1A2, genotype was associated with different amounts of caffeine intake. Compared with persons consuming 200-400, and >400 mg caffeine/d, respectively. The association was more pronounced among current smokers than among nonsmokers (P for interaction = 0.07). Persons with the ADORA2A TT genotype also were significantly more likely to consume less caffeine (ie, <100 mg/d) than were carriers of the C allele [P=0.011 (nonsmokers), P=0.008 (smokers)]. Our findings show that the probability of having the ADORA2A 1083TT genotype decreases as habitual caffeine consumption increases. This observation provides a biologic basis for caffeine consumption behavior and suggests that persons with this genotype may be less vulnerable to caffeine dependence.

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Author and article information

Contributors

M. R. Alcorta-García:

ORCID: https://orcid.org/0000-0001-5909-4871

mario.alcorta@tec.mx

C. N. López-Villaseñor:

ORCID: https://orcid.org/0000-0002-5692-4363

claudia.n.lopez@tec.mx

G. Sánchez-Ferrer: gasafe79@gmail.com

H. Flores-Mendoza: dr.homerofloresm@gmail.com

F. Castorena-Torres:

ORCID: https://orcid.org/0000-0002-1157-0004

fcastorena@tec.mx

M. A. Aguilar-Torres: mike.aat@hotmail.com

C. M. Sepúlveda-Treviño: ceyla93@hotmail.com

J. A. Hernández-Hernández:

ORCID: https://orcid.org/0000-0003-4556-7257

j.a.hernandez@tec.mx

R. C. López-Sánchez:

ORCID: https://orcid.org/0000-0002-6200-1397

lopezsanchezr@tec.mx

V. J. Lara-Díaz:

ORCID: https://orcid.org/0000-0002-1498-8561

lara-diaz.vj@tec.mx

Journal

Journal ID (nlm-ta): Mol Cell Pediatr

Journal ID (iso-abbrev): Mol Cell Pediatr

Title: Molecular and Cellular Pediatrics

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Electronic): 2194-7791

Publication date (Electronic): 1 June 2020

Publication date PMC-release: 1 June 2020

Publication date Collection: December 2020

Volume: 7

Electronic Location Identifier: 4

Affiliations

[1 ]GRID grid.419886.a, ISNI 0000 0001 2203 4701, Tecnologico de Monterrey, , Escuela de Medicina y Ciencias de la Salud, ; Avenida Ignacio Morones Prieto 3000 poniente, Colonia Doctores, CP 64710 Monterrey, Nuevo León México

[2 ]GRID grid.415745.6, ISNI 0000 0004 1791 0836, Hospital Regional Materno Infantil, Secretaria de Salud, , Gobierno del Estado de Nuevo León, ; Avenida San Rafael 450, Colonia San Rafael, CP 67140 Ciudad Guadalupe, Nuevo León México

Author information

M. R. Alcorta-García https://orcid.org/0000-0001-5909-4871

C. N. López-Villaseñor https://orcid.org/0000-0002-5692-4363

F. Castorena-Torres https://orcid.org/0000-0002-1157-0004

J. A. Hernández-Hernández https://orcid.org/0000-0003-4556-7257

R. C. López-Sánchez https://orcid.org/0000-0002-6200-1397

V. J. Lara-Díaz https://orcid.org/0000-0002-1498-8561

Article

Publisher ID: 96

DOI: 10.1186/s40348-020-00096-3

PMC ID: 7261717

PubMed ID: 32476096

SO-VID: 8bc5a2eb-0012-4da0-86a3-1a17e7aad740

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 9 September 2019

Date accepted : 18 May 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100004961, Instituto Tecnológico y de Estudios Superiores de Monterrey;

Award ID: CAT00222

Custom metadata

Keywords: infant, premature,premature birth,caffeine,cytochrome p-450 enzyme system,cytochrome p-450 cyp1a2 inducers,cytochrome p-450 cyp1a2 inhibitors,cytochrome p-450 cyp2e1 inducers,cytochrome p-450 cyp2e1 inhibitors

Data availability:

Keywords: infant, premature, premature birth, caffeine, cytochrome p-450 enzyme system, cytochrome p-450 cyp1a2 inducers, cytochrome p-450 cyp1a2 inhibitors, cytochrome p-450 cyp2e1 inducers, cytochrome p-450 cyp2e1 inhibitors

Modulation of CYP2E1 metabolic activity in a cohort of confirmed caffeine ingesting pregnant women with preterm offspring

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Most cited references 27

Caffeine therapy for apnea of prematurity.

Food sources and intakes of caffeine in the diets of persons in the United States.

Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption.

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